卡巴胆碱对烧伤休克犬肠内补液时肠组织缺血／再灌注损伤的影响

The effect of carbachol on ischemia/reperfusion injury in gut during enteral fluid resuscitation of burn shock in dogs

目的探讨卡巴胆碱（CAR）对烧伤休克期肠内补液时肠缺血／再灌注损伤的保护作用。方法18只成年雄性Beagle犬被随机分为3组，每组6只。采用凝固汽油燃烧法造成50％总体表面积（TBSA）Ⅲ度烧伤模型。伤后无治疗（不补液组）或于伤后30min开始从十二指肠造口分别输入葡萄糖-电解质溶液（GES组）或含CAR的GES（20btg／kgCAR溶于GES，GES／CAR组），伤后8h内输液量依据Parkland公式计算。检测伤前和伤后1、2、4、6、8h小肠黏膜血流量（IMBF）及血浆肿瘤坏死因子-α（TNF—α）含量。伤后8h处死动物，取空肠组织用干湿重法测定小肠组织含水量；并测定一氧化氮合酶（NOS）、丙二醛（MDA）、髓过氧化物酶（MPO）、黄嘌呤氧化酶（XOD）水平。结果各组伤后IMBF均显著降低，TNF—α显著升高；伤后4h起GES组IMBF显著高于不补液组，6h后显著低于GES／CAR组（P均〈0．01）；不补液组与GES组TNF—α含量差异无统计学意义，但伤后2h和4h均显著高于GES／CAR组（P均〈0．01）。伤后8hGES组NOS、MDA、MPO和XOD均显著高于不补液组，而GES／CAR组分别比GES组低26．0％、17．1％、50．0％和19．2％，差异均有统计学意义（P〈0．05或P〈0．01）。GES／CAR组肠组织含水量也显著低于GES组（P〈0．01）。结论CAR能有效减轻烧伤犬肠内补液时肠组织缺血／再灌注损伤，机制可能与增加肠黏膜血流，抗炎和抑制XOD活性，减少炎症因子和氧自由基生成有关。

Objective To investigate the effect of carbachol （CAR） on ischemia/reperfusion （I/R） injury in gut during enteral fluid resuscitation of burn shock. Methods Eighteen male Beagle dogs subjected to a 50% total body surface area （TBSA） full-thickness flame injury were randomized to three groups： no resuscitation （NR） group, enteral fluid resuscitation with glucose-electrolyte solution （GES, GES group）, and enteral fluid resuscitation with GES containing CAR （20 μg/kg, GES/CAR group）. The delivery rate and volume of GES was followed that of Parkland formula 8 hours after burn. Intestinal mucosal blood flow （IMBF） and plasma tumor necrosis factor-α （TNF-α） content were determined at 0, 1, 2, 4, 6 and 8 hours after injury. Animals were sacrificed at the end of 8 hours postburn, and specimens of proximal jejunum was obtained for evaluation of nitric oxide synthase （NOS）, malondialdehyde （MDA）, myeloperoxidase （MPO） and xanthine oxidase （XOD）, and also tissue water content of intestinal tissue. Results 50%TBSA burn injury resulted in obvious decrease of IMBF and elevation of TNF-α in each group. IMBF in GES group was significantly higher than that in NR group from 4 hours after burn, but lower than that of GES/CAR group at 6 hours after burn （all P〈0.01）. There were no statistical differences in plasma level of TNF-α in animals between GES group and NR group, but they were significantly higher than that of GES/CAR group at 2 hours and 4 hours after burn （all P〈0.01）. Enteral resuscitation resulted in markedly higher levels of NOS, MDA, MPO, XOD in GES group compared with those in NR group at 8 hours after burn ;EGS/CAR resuscitation led to a 26.0%, 17. 1%, 50. 0% and 19. 2% decrease in NOS, MDA, MPO and XOD compared with those in GES group （P〈0.05 or P〈0.01）. There was also a lower water content of gut tissues in GES/CAR group compared with the GES group （P〈 0.01）. Conclusion CAR can alleviate gut I/R injury during enteral resuscitation for burn shock, which might be associated with its effects of promoting intestinal blood flow, anti-inflammation and inhibition of oxygen free radical production in gut tissue.